In pharmaceutical delivery systems, it is often required that a drug in powder form be mixed with a diluent in order to be able to deliver the drug to a patient. To date, this is frequently done by injecting the diluent into a vial containing the powder drug, mixing the drug with the diluent and then aspirating the drug in fluid form into a syringe for subsequent injection into the patient. A manual mixing such as this can be cumbersome and inconvenient and can also lead to wastage of some of the drug which may remain in the vial.
Other more automated systems for mixing the drug and diluent have been developed and are shown in U.S. Pat. Nos. 5,817,055 and 5,716,338. In these patents, the mixing of the drug and diluent is achieved in what is known as a by-pass syringe having two compartments; one containing the drug and the other the diluent.
These devices have been used for many years to aseptically package lyophilized or “freeze-dried” medications together with their diluents. In recent years specially coated drug micro-units have been produced in the form of microspheres which release slowly into the bloodstream when administered are also now being packaged in these devices. The packaging of lyophilized drugs requires that the liquid drug admixture be filled into the top chamber so that once frozen, all water will sublimate under vacuum leaving a dried cake of residual drug product. For this reason an aqueous diluent needs to be filled in the lower chamber of the syringe after the freeze drying cycle. The production of powdered products such as microspheres requires that the diluent be filled in the lower chamber first followed by powder filling in the upper chamber. This will ensure that the diluent is well sealed before entering the well isolated powder-filling environment where unwanted powder contamination is a concern.
The preparation for administration in these double chamber by-pass syringes however is much the same and requires that the device always be held vertically with the exit nozzle pointing upwards. The mixing action occurs when the rear plunger is pushed forward very slowly. This movement can be dampened by using a threaded plunger rod so that the user must screw the rod thereby providing a slow controlled upward movement of the rear plunger. This movement moves the entire diluent including the upper plunger upwards into the by-pass area (any fast uncontrolled movement would move the plunger beyond the by-pass area and block flow of the diluent). Continued slow upward movement will cause all of the diluent to flow through the by-pass around the upper plunger and into the upper chamber mixing with drug component and expelling some of the air above it.
At this point the user must stop pressure on the plunger rod and begin swirling or shaking the syringe to ensure dissolution or suspension of the drug. If either component of the admixture contains a surface active agent to promote wetting then excessive foaming can be a problem as well as the problem of entrained air bubbles. After some time and when the admixture is suitably mixed, and foam or bubbles have been allowed to dissipate, then the user can slowly push the plunger rod to expel the air above the drug surface, attach a needle and inject the medication.
Quite apart from the above, there may also be a requirement to remix a mixture which has separated out and needs to be transferred to a syringe type structure.